ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Metabolism and Toxicity of Trichloroethylene and Tetrachloroethylene in Cytochrome P450 2E1 Knockout and Humanized Transgenic Mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects.Annual review of pharmacology and toxicology · 2025Review
- CYP2E1 in 1,4-dioxane metabolism and liver toxicity: insights from CYP2E1 knockout mice study.Archives of toxicology · 2024Article
- Renal Glutathione: Dual roles as antioxidant protector and bioactivation promoter.Biochemical pharmacology · 2024Review
- Developmental trichloroethylene exposure enhances predictive markers of autoimmunity in a sex-specific manner in disease-resistant female mice.Toxicology and applied pharmacology · 2022Article
- Evaluation of Metabolism of a Defined Pesticide Mixture through Multiple In Vitro Liver Models.Toxics · 2022Article
- Performance and Mechanisms of Sulfidated Nanoscale Zero-Valent Iron Materials for Toxic TCE Removal from the Groundwater.International journal of environmental research and public health · 2022Article
- Quantitative Characterization of Population-Wide Tissue- and Metabolite-Specific Variability in Perchloroethylene Toxicokinetics in Male Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Metabolic Signatures of the Exposome-Quantifying the Impact of Exposure to Environmental Chemicals on Human Health.Metabolites · 2020Review
- PBPK modeling of impact of nonalcoholic fatty liver disease on toxicokinetics of perchloroethylene in mice.Toxicology and applied pharmacology · 2020Article
- Cytochrome P450 2E1 and its roles in disease.Chemico-biological interactions · 2020Review
- Genetically Engineered Human Kidney Cells for Real-Time Cytotoxicity Testing In Vitro.Molecular biotechnology · 2020Article
- Trichloroethylene, a ubiquitous environmental contaminant in the risk for Parkinson's disease.Environmental science. Processes & impacts · 2020Article
- Sex-Dependent Effects on Liver Inflammation and Gut Microbial Dysbiosis After Continuous Developmental Exposure to Trichloroethylene in Autoimmune-Prone Mice.Frontiers in pharmacology · 2020Article
- Cytochrome P450 2E1-deficient MRL+/+ mice are less susceptible to trichloroethene-mediated autoimmunity: Involvement of oxidative stress-responsive signaling pathways.Free radical biology & medicine · 2019Article
- Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene.Environmental health perspectives · 2019Article
- Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains.Toxicology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Trichloroethylene (TCE) and tetrachloroethylene (PCE) are structurally similar olefins that can cause liver and kidney toxicity. Adverse effects of these chemicals are associated with metabolism to oxidative and glutathione conjugation moieties. It is thought that CYP2E1 is crucial to the oxidative metabolism of TCE and PCE, and may also play a role in formation of nephrotoxic metabolites; however, inter-species and inter-individual differences in contribution of CYP2E1 to metabolism and toxicity are not well understood. Therefore, the role of CYP2E1 in metabolism and toxic effects of TCE and PCE was investigated using male and female wild-type [129S1/SvlmJ], Cyp2e1(-/-), and humanized Cyp2e1 [hCYP2E1] mice. To fill in existing gaps in our knowledge, we conducted a toxicokinetic study of TCE (600 mg/kg, single dose, i.g.) and a subacute study of PCE (500 mg/kg/day, 5 days, i.g.) in 3 strains. Liver and kidney tissues were subject to profiling of oxidative and glutathione conjugation metabolites of TCE and PCE, as well as toxicity endpoints. The amounts of trichloroacetic acid formed in the liver was hCYP2E1≈ 129S1/SvlmJ > Cyp2e1(-/-) for both TCE and PCE; levels in males were about 2-fold higher than in females. Interestingly, 2- to 3-fold higher levels of conjugation metabolites were observed in TCE-treated Cyp2e1(-/-) mice. PCE induced lipid accumulation only in liver of 129S1/SvlmJ mice. In the kidney, PCE exposure resulted in acute proximal tubule injury in both sexes in all strains (hCYP2E1 ≈ 129S1/SvlmJ > Cyp2e1(-/-)). In conclusion, our results demonstrate that CYP2E1 is an important, but not exclusive actor in the oxidative metabolism and toxicity of TCE and PCE.
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